title: Aspirin prodrugs: synthesis of 2-substituted 2-methyl-4H-1,3-benzodioxin-4-ones and their screening for prodrug potential.
abstract: A series of new 2-substituted 2-methyl-4H-1,3-benzodioxin-4-ones 1 have been synthesized and fully characterized. This study involves fifteen compounds of which fourteen are orthoesters, containing tertiary aliphatic alkoxy groups. One compound contains a tert-butylperoxy group and one a 3 beta-cholesteryloxy group in the 2-position. The hydrolysis of these compounds 1 was followed in enzymatic and non-enzymatic media to clarify whether they are true prodrugs of aspirin. Two compounds 1 were additionally tested in vivo as potential topical keratolytics.
authors.affiliation: Department of Organic Chemistry, University of Aarhus, Denmark.
authors.forename: K K
authors.initials: KK
authors.lastname: Nielsen
authors.forename: A
authors.initials: A
authors.lastname: Senning
mesh_terms: D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000097:blood / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004147:Dioxins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D006868:Hydrolysis; D007641:Keratolytic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004147:Dioxins; D007641:Keratolytic Agents; D011355:Prodrugs; D001241:Aspirin